1. Field of the Invention
The present invention relates to functionalized polymeric materials and, more particularly, relates to water insoluble controlled density polyamines which are cross-linked. The subject polyamines swell at pH values of about 8 or less but do not swell at pH values above about 8. In addition, such polyamines can be functionalized to modify the properties thereof. For example, the polyamines can be quaternized rendering the polymeric material swellable at pH values greater than about 8, and/or a drug can be attached to such polyamines.
2. Related Art
It is well known in the art to convert olefins to aldehydes having one additional carbon atom by contacting a C.sub.2 to C.sub.20 monoolefin or a C.sub.5 to C.sub.5000 nonconjugated polyolefin with hydrogen and carbon monoxide in the presence of a catalyst based on cobalt or rhodium metal. See, for example, U.S. Pat. No. 4,871,878.
It is also known, as disclosed in U.S. Pat. No. 3,383,426, to hydroformylate polymers utilizing hydrocarbon-soluble phosphine and phosphite catalyst complexes which include a Group VIII transition metal and at least one ligand consisting of a carbon monoxide molecule.
The principle of obtaining amines starting from an olefin, hydrogen carbon monoxide and a primary or secondary amine is known. Various techniques embodying this principle have been described using catalysts of various kinds. Such techniques are generally referred to as aminomethylation reactions.
Helvetica Chemical Acta, Volume 53, pages 1440 to 1445 (1971) U.S. Pat. No. 3,947,458 (1976), teach catalytic aminomethylation of olefins employing a rhodium oxide catalyst, an iron carbonyl catalyst and a mixed rhodium oxide/iron carbonyl catalyst.
U.S. Pat. No. 4,096,150 (1978) discloses a process for the manufacture of tertiary amines wherein an olefin, hydrogen, CO and secondary amine are reacted in the presence of a coordination complex catalyst of a Group VIII metal and a ligand, the donor atom of which is oxygen, nitrogen or sulfur.
Amines can be prepared from a dehydrogenated paraffin feedstock reacted with a nitrogen-containing compound, carbon monoxide and hydrogen in the presence of a rhodium or ruthenium-containing compound. See U.S. Pat. No. 4,179,469.
It is known to prepare tertiary amines by reacting a long-chain olefin with carbon monoxide, hydrogen and a primary or secondary amine in the presence of a catalyst comprising rhodium and/or ruthenium and using a specifically outlined solvent which allows for phase separation. See U.S. Pat. Nos. 4,448,996 and 4,250,115.
U.S. Pat. No. 4,207,260 (1980) to Imai discloses tertiary amines prepared by reacting an aldehyde, hydrogen and a nitrogen-containing compound in the presence of rhodium or ruthenium-containing catalyst at temperatures in the range of 50.degree.-350.degree. F. and a pressure in the range of 10 to 600 atm. Another U.S. patent to Imai (U.S. Pat. No. 4,220,764 1980) teaches preparation of tertiary amines by a similar process except that the catalyst comprises a rhodium chloride rather than a rhodium carbonyl.
It is also known that phosphite ligands can be used to stabilize unsaturated rhodium species in order to hydroformylate otherwise unreactive olefins under mild conditions. No ruthenium carbonyl is employed in this process. See for example, Van Leeuwen et al report in an article in the J. Organometallic Chem. 258 (1983) 343-350.
In J. Org. Chem. 47, 445 (1991), Jachimowicz et al disclose various approaches which have been used in attempts to devise a one-step, efficient and general conversion of olefins to amines. Among the catalysts are iron pentacarbonyl, rhodium oxide, ruthenium/iron carbonyl and iridium catalysts.
In U.S. Pat. No. 4,297,481, Jachimowicz discloses a process for forming a polymeric polyamine/amide wherein said amino/amido nitrogens are positioned in the polymer backbone by contacting a monomeric nitrogen compound which has at least two labile hydrogens bonded to the nitrogen atoms therein, a monomeric hydrocarbon compound containing at least two olefinic groups therein, carbon monoxide and water in the presence of a catalytic amount of a rhodium-containing compound. This invention describes the use of ammonia or primary amines. The preparation of polymers with pendant amine and amide groups is also described in U.S. Pat. No. 4,312,965. These polymers are prepared from polymeric polyolefins, carbon monoxide, and monomeric nitrogen compounds as described previously. Again, rhodium or a rhodium-containing compound serves as the catalyst.
U.S. Pat. No. 4,503,217 teaches a process for preparing polymeric polyamines from polybutadiene, ammonia and primary or secondary amines in the presence of a catalyst system comprising a ruthenium-containing catalyst and a dimethyl formamide solvent which provides a two-phase liquid product, allowing for easy preparation of the product polyamine.
A review of prior art indicates that others have prepared similar materials such as polymeric polyamines. Specifically, poly(butadienes) having high vinyl content that comprise a high concentration of the 1,2-polybutadiene building block have been reacted with synthesis gas and secondary dialkylamines to provide dialkylaminemethylated polymers with a high degree of functionality. Others have formed similar materials but have been unable to functionalize the internal olefinic groups prevalent in lower cost polybutadiene that comprise in the main the 1,4-polybutadiene building block. Until recently, a good method has not generally been available for causing a reaction to occur in the internal olefin groups prevalent in lower cost polybutadiene. Very often these internal double bonds have remained in the final product or have been hydrogenated.
U.S. Pat. No. 4,657,984 discloses preparation of polymeric polyamines from CO, hydrogen, polymeric olefins and secondary amines utilizing as catalysts ruthenium or rhodium phosphines. It is stated that use of these particular catalysts facilitates reaction and hence functionalization of internal as well as vinyl olefin groups.
Thus, the state of the art for preparing polymeric secondary and tertiary polyamines teaches an aminomethylation reaction wherein the vinylic olefins and internal olefins can be reacted utilizing various catalysts under a variety of conditions. However, these reactions are significantly different than reductive amination reactions because there is no teaching in the prior art regarding aminomethylations on how to control the degree of functionalization, or the functional density, of either the polyaldehyde or of the polyamine prepared therefrom. For certain applications, it is desirable to control the functional density of the resulting polyamines. For example, it is desirable for certain applications, such as drug delivery, to further functionalize such polyamines utilizing residual unsaturation in the polymer material to link a drug to the polymer system. In addition, it is desirable, in certain circumstances, such as in drug delivery, to modify certain properties or characteristics of the polymer system, such as, for example, swelling characteristics by further functionalization such as by increasing the degree of cross-linking. Further functionalization of prior art polyamines utilizing remaining olefin groups is difficult, and in some cases is not possible because there is no appreciable degree of control over the reaction of such olefin groups in the process.
Accordingly, the present invention is directed to water insoluble controlled density polyamines which are cross-linked. These polyamines are particularly suitable for use in site specific delivery of drugs.